Use this section to discuss your experiences with prescription drugs, iron injections, and other medical interventions that involve the introduction of a drug or medicine into the body. Discuss side effects, successes, failures, published research, information about drug trials, and information about new medications being developed.

Important: Posts and information in this section are based on personal experiences and recommendations; they should not be considered a substitute for the advice of a healthcare provider.

I've been taking very small doses (2-3.75.mg) of mirtiazpine for the past 3 years to cope with ineffective CPAP. It really would help me sleep decently on nights I used it. Aware of the perils of neurotransmitter affecting drugs, I made sure to use it only 1-2 twice a week at most and very small doses. But then since the course of this winter my calves developed involuntarily tensing at rest at night. Now the past month it has progressed to my arms and occurs all day (though least in the early AM and early afternoon.

I've also been taking melatonin everyday for the past 10 years. Which I recently found out the 3mg doses and whatnot are just way too much. I see serotonin affecting ADs like mirtaz can worsen RLS and it indirectly increases dopamine, and melatonin is opposite to dopamine, so perhaps since I've been loading up on melatonin for so long, I've driven down my dopamine production by both melatonin and mirtaz and that explains my current symptoms?

I can actually feel when I lie there at night the dopamine rush that happens around 3-4am. Everything feels cool and calms down a bit. Am I too damaged now? I pray this isn't permanent. I can't sleep, I don't want to rely on meds anymore they don't work that long anyway.

All kind of drugs can worsen RLS but antidepressants like mirtazapine and in general als tri-cycli and tetra-cyclic antidepressents can worsen RLS ... even in very small doses and even when you take it only once.

My experience is that even melatonine and melatonine-receptor agonists unfortunately can worsen RLS.

I see serotonin affecting ADs like mirtaz can worsen RLS and it indirectly increases dopamine, and melatonin is opposite to dopamine, so perhaps since I've been loading up on melatonin for so long, I've driven down my dopamine production by both melatonin and mirtaz and that explains my current symptoms?

No. That's really not how it works. Dopamine is also not the opposite of melatonin. It is just something different.

What you describe as "dopamine rush" ... I have a similar experience around same hours.

I guess it has more to do that our inner clock is completely out of sync and that maybe is a part of RLS or is not.

My observation is that there are some patients with RLS who still seem to have a good working inner clock but most patients have some kind of desync and suffer some hyper-alertness. The big problem is that when you have RLS, basically all the drugs who normally can be used to put you to sleep like mild doses of neuroleptics or antidepressants like mirtazapine won't be tolerated.

I am currently exploring alternatives treatment for this issue and plan to see new doctor for it but so far I have no idea what could help long term except exposing yourself to lot of sunlight, especially in the first half of the day.

Well dopamine is the opposite not chemically but in the circadian ryhtyhm. When you are producing melatonin your body is reducing dopamine and visa versa. Peak dopamine production is in the early morning hours, which is why RLs suffers get most relief in morning/earlier in the day. Dopamine production hits peak low at night, while melatonin is peak. See here: https://www.sciencedaily.com/releases/2 ... 225725.htm

But yeah, the rest was just my hypothesis. Mirtaz stimulates dopamine production indirectly, and Melatonin reduces dopamine production also in the pineal. So maybe both with keeping dopamine down and stimulating it with mirtaz..maybe my bodys natural production took a dump but yeah that was just my guess /shrug.

In the past like 4 weeks though I've taken TOTAL like 5mg mirtaz. So I'm beginning to think these symptoms are unrelated and this is a new problem I have to deal with =/. I just don't know how you guys manage this. Even when I was withdrawing my benzos my sleep wasn't this bad. The symptoms started before I tried to remove both mela and mirtaz from my daily regime. But that doesn't seem to help either.

RLS involves more than just symptoms created by an excess of dopamine. It has been shown to also involve both adeonsine and glutamate. It appears that brain iron deficiency results in the down regulation of adenosine receptors. Adenosine levels are supposed to rise during the day as we burn ATP for energy. The buildup is what makes us tired and sleepy. This is supposed to result in a decrease in dopamine, which makes us lethargic, and glutamate, which allows us to fall asleep. But when the adenosine receptors don't allow the adenosine to cause a reduction in dopamine and glutamate, it leaves us tired, but we still have a need to stay active and moving and we cannot fall asleep.

The theory is that dopamine agonists help force a reduction in dopamine, which allows us to stop moving, and gabapentin (and like meds plus benzos) allow the glutamate levels to drop so that we fall can asleep. Opioids work in other ways and increasing ferritin levels helps some to up regulate the adenosine receptors so that they can do their job of allowing things to work more normally. Current research is also looking at new ways to influence the adenosine receptors to work normally, even with brain iron deficiency.

So, it is all interconnected. You cannot just focus on dopamine or glutamate because doing so is continuing to just treat the symptoms and not the disease.

The latest research indicates that the cause of RLS is tied to brain iron deficiency. The problem is that low iron in the brain can either be due to low iron stores in the body (as measured by ferritin levels and regular blood tests) or it can be due to an inability to get iron across the blood-brain barrier (which is the problem that I have).

So, there can be multiple reasons for low iron in the brain, but our symptoms can be traced to that one condition.

It is actually conceivable that there could be more direct ways of getting the brain iron levels up. The simplest perhaps would be injecting an iron compound directly into the cerebrospinal fluid during a spinal tap.